Photodynamic therapy (PDT) seems destined for clinical application for a variety of solid tumors. PDT involves the use of a photosensitizer which can be activated in vivo by penetrating light. As in most new therapies, many basic questions regarding mechanisms of action are poorly understood. This proposal addresses certain these questions. It has the following aims: 1. Mechanism of uptake and retention of the active photosensitizer in hematoporphyrin derivative, tentatively identified as dihematoporhyrin ether (DHE); 2. Why the vasculature of tumors is a major target of PDT; 3. What tissue factors influence tissue response to PDT; 4. Can the drug and light dose be varied to improve therapeutic ratio in PDT; 5. To improve instrumentation for detection of very small or very deep tumors via porphyrin fluorescence.